Peter Alping

Abstract

OBJECTIVE: To assess safety outcomes for the induction therapies alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT), compared to non-induction disease-modifying therapies.

METHODS: We performed a population-based cohort study linking the Swedish Multiple Sclerosis Register to national healthcare registers. Alemtuzumab, AHSCT, and a matched reference group of non-induction therapies (natalizumab, dimethyl fumarate, rituximab, fingolimod) were included if started between 2008 and 2017. Main outcomes were death, thyroid disease, non-thyroid autoimmune disease, and infection.

RESULTS: We identified 132 alemtuzumab-treated and 139 AHSCT-treated (68% Cy/ATG, 32% BEAM/ATG) patients, together with 2486 matched patients treated with non-induction therapies. Four patients in the alemtuzumab group died (incidence rate [IR] per 1000 person years=8.6, 95% confidence interval [CI]=2.3-22.0) compared to one patient in the AHSCT group (IR=1.7, 95% CI=0.0-9.6) and a mortality rate in the reference group of 0.7 (95% CI=0.3-1.3). Thyroid disease was most frequent in the alemtuzumab group (IR=109, 95% CI=75-154), but also occurred more often for AHSCT (IR=34, 95% CI=18-56) compared to the reference (IR=5.3 95% CI=3.9-7.1). The incidence of non-thyroid autoimmune disease was similar in all groups. IR for infection diagnosed ≥6 months from therapy initiation was 53 (95% CI=30-87) for alemtuzumab, 108 (95% CI=75-150) for AHSCT, and 51 (95% CI=46-57) for the reference.

CONCLUSION: We confirmed a high incidence of thyroid disease in alemtuzumab- and to a smaller extent also AHSCT-treated patients, and found a higher incidence of infection for AHSCT, compared to both alemtuzumab and non-induction therapies. The incidence of non-thyroid autoimmune disease was low for both therapies.

CLASSIFICATION OF EVIDENCE: This study provides Class III evidence of an increased risk of thyroid disease with alemtuzumab and an increased risk of infection with AHSCT treatment.